Predicting Immunotherapy Responses: Scientists Discover Key Factors
Immunotherapy is the latest weapon in the arsenal against cancer, but it doesn't work for everyone or every cancer type. To address this problem, researchers from Johns Hopkins have discovered a specific set of mutations in cancerous tumors that suggest how responsive the tumor will be to immunotherapy.
In their study published in Nature Medicine, the researchers found a subset of mutations within the overall tumor mutation burden (TMB). These mutations, called "persistent mutations," are less likely to disappear as the cancer evolves, making the tumor more visible to the immune system. This visibility leads to a better response to immunotherapy, resulting in sustained tumor control and longer survival.
Previously, doctors calculated the TMB to determine how well a tumor would respond to immunotherapy. However, the researchers found that persistent mutations are a better indicator of a tumor's responsiveness to immunotherapy compared to the overall TMB. By identifying the persistent mutations in a tumor, doctors can more accurately select patients for immunotherapy and predict treatment outcomes.
The researchers found that the mutations they identified were in the DNA polymerase epsilon and delta genes, known as POLE and POLD1 mutations. These mutations affect the proofreading function during DNA replication, causing an extremely high TMB in tumors with POLE/POLD1 mutations.
High TMB is associated with an increased neoantigen load, making the tumor more recognizable and vulnerable to attack by the immune system when treated with immunotherapies. Therefore, testing for POLE/POLD1 mutations can help predict which tumors are likely to respond well to immunotherapy strategies.
In the future, high-throughput, next-generation sequencing techniques can be used to study patients' mutational spectrum, allowing doctors to categorize patients by their likelihood of response to immunotherapy. This could potentially lead to tailored treatment strategies for cancer patients, increasing the effectiveness of immunotherapy and improving outcomes.
- In the field of medical-conditions like cancer, the identification of persistent mutations within a tumor mutation burden (TMB) can be a more effective indicator than the overall TMB in determining a tumor's responsiveness to immunotherapy.
- Specific mutations, such as those in the DNA polymerase epsilon and delta genes (POLE and POLD1), can significantly increase a tumor's neoantigen load, making it more vulnerable to immunotherapy.
- With advancements in science and health-and-wellness, high-throughput, next-generation sequencing techniques may enable doctors to categorize patients based on their likelihood of response to immunotherapy, potentially leading to more effective and personalized treatments for cancer patients.
